WO2016038641A1

WO2016038641A1 - Needleless injection device with dosing

Info

Publication number: WO2016038641A1
Application number: PCT/IT2015/000219
Authority: WO
Inventors: Mario Geat; Luciano Dornik
Original assignee: Brovedani S.P.A.
Priority date: 2014-09-11
Filing date: 2015-09-11
Publication date: 2016-03-17

Abstract

A drugs transdermic dosing device (1), comprising a body or fixed portion (2) with a piston (33) and a nozzle (37) for dosing a drug, a movable or swiveling portion (4), associated with said fixed portion (2) and usable to set the dose of drug, and at least one button (22) for activating the device (1 ), which is connected with a punch (31) acting on said piston (33). A bushing (3) is placed between said fixed portion (2) and said movable portion (4), said bushing (3) having a seat (24) for housing at least one cylindrical ring (5), which is divided into a numbered lower portion (25) and an upper portion (26) having a dowelling surface and which is activable from the outside. The cylindrical ring (5) has a lower base, where there are formed a plurality of first conical imprints (28), which are adapted to be engaged by a first probe (7) mounted in the fixed portion (2), and an upper base, where there are formed a plurality of second conical imprints (38), which are placed axially with respect to the first conical imprints (28) and which are adapted to be engaged by a second probe (9), mounted within said movable portion (4) and placed parallel and opposite to said first probe (7).

Description

NEEDLELESS INJECTION DEVICE WITH DOSING

The present invention generally relates to a drugs transdermic dosing device and, in particular, to an insulin transdermic dosing device, which is able to substantially improve the method of treatment of diabetes by means of a better absorption of the drug.

More particularly, the invention relates to a new structure of a drugs transdermic dosing device, whose technical features allow to improve the drug dosing method.

Transdermic dosing is a method of drugs dosing that is becoming more used in the medical field both for the practical advantages of the method (no presence of needles and no risks of phobias, no risk of injuries and no disposal problems) and for the clinical benefits of the method (the absorption of the drug is thus greatly improved).

The known drugs transdermic dosing device are constituted by spray injectors, which inject the drug into the subcutaneous tissue through a microscopic nozzle, thus ensuring a fast and homogeneous absorption of the drug.

The constructive features of certain devices made with an injector (nozzle, piston and cylinder) which is made of steel (rather than plastic) ensure high performance and allow the device to be reusable for an indefinite number of times.

However, the above known devices do not allow a visual check of the amount of drug which is loaded and therefore it is necessary that the quantity loaded is correct; furthermore, it is necessary to take into account of systematic errors in charging phase, due for example to the volumes and to the dimensions of adapters needed for loading the drug.

Another critical feature of said known devices is the fact that the strength of the drug dosing is not proportional to the quantity of the drug which is loaded, since the compression of the load spring does not depend on the amount of drug that is loaded, whereas the device which is the object of the invention shows a force which is directly proportional to the rotation of the adjusting screw and therefore it provides for a practical and accurate method for showing the quantities of drug loaded by the device.

Moreover, since the device is characterized by a good charge and dosing accuracy and considering that said device is also intended for use on children patients, it is desirable to have a system which allows to measure even the half-unit of loaded drug. In the context of the above mentioned requirements, therefore, an object of the present invention is to obviate the above drawbacks and, in particular, to provide a drugs transdermic dosing device, which is able to improve the drug's dosing and assimilation methods, with respect to the prior art.

Another object of the invention is to provide a drugs transdermic dosing device, for example for dosing human or analogous insulin, which is high reliable, efficient, functional and less expensive than the known devices. These and other objects, according to the present invention, are achieved by providing a drugs transdermic dosing device according to the appended claim 1 ; other technical features are described in the dependent claims. Advantageously, the drugs transdermic dosing device (atomizing device), which is the object of the present invention, comprises a fixed body, which has internally a piston axially connected to a punch and a nozzle for dispensing the drug, a movable portion, associated to the fixed portion and usable to set the dose of drug to be provided by means of the displacement of the punch and of the piston and through the activation of a spring connected to the punch, and at least one device activation button, which is associated to the punch and which acts on the dispensing piston. In other words, the device of the invention is constituted by an injector without needle, which is able to perform intracutaneous or transdermic injections of liquid by using a jet of high pressure fluid, resulting from the action of a plunger elastically pre-loaded through a spring, which provides at the output, in correspondence of a small nozzle, a cloud of droplets of the drug, which is thus pushed inside the skin of the patient.

Consequently, the pressure and the output speed of the droplets of the drug allow the same drug to penetrate inside the skin, so as to affect the capillaries and the lymphatic vessels of the dermis.

Practically, the dose of the drug is introduced into the device before each application, then the device is placed on the skin of the patient and, through the pressure of a button, the injection is carried out on the patient's skin with a force which is proportional to the dose of drug loaded during the arming of the device.

The device can also have a safety button, which is able to avoid unwanted injections.

The device is an entirely mechanical device and the charge of the drug is performed by aspirating the liquid inside, through the rotation of a predetermined portion of said device that causes a com pression of the spring; furthermore, a simple and practical dosing device accurately shows the drug units which have been loaded.

The drug container is an integral part of the device and the operations of loading and injection into the skin of the patient may be carried out without removing or moving parts of the device, which, once used, is entirely reusable.

Finally, the device of the present invention is easily removable for a complete cleaning and/or disinfection of the portions which goes into contact with the drug and with the patient's skin.

Therefore, said device, which can also be made in small sizes and/or miniaturized, allows to use ready liquid drugs, which are injected in form of particles of infinitesimal size and only in the superficial layers of the dermis, where it is not possible to cause bruising, thanks to the particular shape of the nozzle, which is extremely small, and thanks to the spring's load; the liquid drug thus exits at great speed from the nozzle hole, with an extended shape of the jet, so as to completely eliminate the pain for the patient and to allow a better distribution of the drug on the layers of the dermis.

Further characteristics and advantages of a drugs transdermic dosing device according to the invention will be more clear from the following description relating to a preferred embodiment of the invention and from the enclosed drawings, in which:

- figure 1 shows a cross-sectional view of the drugs transdermic dosing device, according to the present invention;

- figure 2 shows an enlarged view of a rear portion of the drugs transdermic dosing device of fig. 1 , according to the present invention;

- figure 3 shows an enlarged detail of fig. 2, according to the invention;

- figure 4 shows an enlarged detail of fig. 3, according to the invention, where a control window with two different openings is shown;

- figure 5 shows a front view of the detail of fig. 4, according to the invention, where a bushing with a recess for housing a numbered ring nut is shown;

- figure 6 shows a front view of a damping plate coupled to the bushing of fig. 5, according to the present invention;

- figure 7 shows a cross-sectional view of fig. 6, according to the invention;

- figure 8 shows a sectioned front view of the charging body provided in the device of fig. 1 , according to the present invention;

- figure 9 shows a cross-sectional view of fig. 8, according to the invention;

- figures 10, 11 , 12, 13, 14, 15, 16 and 17 show a plurality of views of details of a numbered ring nut and of the probes used in the device of fig. 1 , according to the present invention;

- figure 18 shows a cross-sectional view of a detail of the device of fig. 1 , according to the present invention;

- figure 19 shows a front view of the detail of fig. 18, according to the present invention;

- figure 20 shows a first embodiment of an anti-unscrewing system used in the device of fig. 1 , according to the invention;

- figure 21 shows a second embodiment of an anti-unscrewing system used in the device of fig. 1 , according to the invention.

With reference to the above mentioned figures, with 2 is indicated a body or a fixed portion of the atomizing device 1 for drugs transdermic dosing, according to the present invention, with 4 is indicated a movable or swiveling portion (charging body), with 22 is indicated an activation button, with 23 is indicated a safety button, while with 27 is indicated a cap, usually made of elastic and/or yieldable material, such as rubber, which is provided to protect the dispensing nozzle 37.

The charging body 4 can be connected to a container (not shown in the attached figures), which is filled with the liquid drug to be dispensed and which is mounted in a position parallel to the fixed portion 2 through a specific adapter and/or an extractor (not shown in the attached figures). In particular, the liquid drug, such as, for example, human insulin or the like, that is contained in an ampoule or in a standard vial, can be introduced into the container firstly by inserting the ejector in a rear portion of a piston placed inside the container and then by removing the metal cap from the top of the vial and pushing the shaped adapter into contact with the protection cap of the vial; the shaped adapter is usually made in order to facilitate the tightening on the neck of the ampoule and, at the same time, to cause the drilling of the protection cap.

At this point, the top of the shaped adapter is introduced into the container, on the side opposite to the extractor, and then it is enough to rotate the container by 90°, slightly forcing the resistance due to the compression of a rubber cylinder, and use the extractor in order to extract, by means of the piston, the liquid drug from the vial, and to suck it into the cylindrical container through a hole in the rubber cylinder; at the end of this operation the container is removed by turning and pulling it out from the previous position, so that the liquid drug can not leak, also thanks to the presence of a special seal of the piston.

The vial remains attached to the adapter and the insulation between the inside and the outside of the vial is secured by a cover cap arranged above the adapter; moreover, by removing the extractor from the rear portion of the piston, the extractor itself and the adapter can be put away for a new filling operation of the container.

Finally, the container of the liquid drug, ready for use, may be fixed to the fixed portion 2 of the device 1 through a support bracket and a buffer which is applied to the charging body 4.

In order to load the liquid drug within the device 1 , starting from the above mentioned rest position, the container is removed from the mounting bracket and from the buffer, as well as the protection cap 27 of the fixed portion 2 of the device 1 is removed from the nozzle 37; furthermore, the container is inserted on the nozzle 37 through a rotation of said container by 90° and by providing a suitable pressure.

The drug is thus loaded within the device 1 after that the movable or swiveling portion (charging body) 4 of the device 1 is rotated and retains the fixed portion 2; in this way, the rotation of the swiveling portion 4 causes the screwing of a threaded nut 29 on the punch 31 , which has a threaded screw 30 near its end portion, with the result that, since the punch 31 cannot rotate on its own axis, said punch 31 moves backward so as to compress the spring 32.

The backward movement of the punch 31 causes a similar backward movement of the piston 33, thus causing a depression inside an injection chamber 18, which is placed near the nozzle 37, so that the liquid drug passes from the container, placed in front of the fixed portion 2, to the injection chamber 18 when the container is firmly secured to the nozzle 37 of the fixed part 2 of the device 1.

When the desired units of drug have been loaded into the device 1 , it is possible to simply remove the container from the nozzle 37 of the head 40 of the device 1 and place the container in a position parallel to the fixed part 2; the device 1 is thus ready for dispensing drug within the skin of the patient.

During the dispensing phase, which directly follows the loading of the drug within the device 1 , the protective cap 27 of the nozzle 37 is removed from the head 40 of the fixed part 2 and, in order to effect the atomization of the drug inside the patient's skin, it is enough to press the button 22 taking care to maintain the device 1 in an orthogonal position with respect to the skin surface of the patient, so as to avoid the leakage of liquid, and after releasing the safety button 23 from an inserted position to a disengaged position.

In particular, to allow the operation of the button 22, it is necessary to push the safety button 23 to allow the lowering and the unlocking of the blocking ball 41.

When the button 22 is pressed, the drum 42 flows inside of its seat and the threaded nut 29, which is retained by a special component, is thus free to release the screw 30.

Moreover, the punch 31 , which is pushed by the pre-loaded spring 32, moves the piston 33 forward into the injection chamber 18, so that the drug can be pushed outside through a small hole drilled in the nozzle 37 of the head 40.

After the nebulization, the piston 33 and the punch 31 remain in the rest position and therefore, by releasing the activation button 22, the spring 44 pushes backwards again the above button 22 and the drum 42, which, moving backwards, force the threaded nut 29 to move on the thread of the punch 31 , thus restoring the starting conditions.

After having dispensed the drug, the safety button 23 must be pressed into an insertion position, the dosing meter must be reset and the protective cap 27 must be re-applied on the nozzle 37 of the head 40.

Thanks to the particular shape of the nozzle 37, which can be considered as the sole responsible for the shape of the liquid drug's jet, it is possible to obtain an effective dispensing of the drug and therefore an effective absorption inside the patient's skin.

In particular, the nozzle 37 has a cylindrical body which is shaped at one end and has an outlet hole which is extremely small and suitably shaped, so as to realize an extended and not elongated drug's jet; the liquid drug thus exits at a great speed from the hole, so as to eliminate the pain for the patient and to ensure a better distribution of the drug into the dermis. Furthermore, the nozzle hole 37 has a substantially cylindrical shape with an height which is relatively short with respect to the overall length of said nozzle 37, while the inner walls of said nozzle 37, which convey the liquid drug to the dispensing hole, have a conical shape, made in such a way that the angle formed by each inner wall with the longitudinal axis of the nozzle 37 is substantially equal to 45°.

It is thus possible to obtain an optimal distribution of the liquid drug's jet, which can thus be dispensed in an effective way, so as to reach only the surface layers of the dermis, thus avoiding bruising or pain to the patient and ensuring an optimum absorption,

According to the present invention, a bushing 3 is inserted into the body or the fixed portion 2 of the device 1 or is integral with the body 2 by molding or machining processing.

Said bushing 3 has a truncated-cone shape and is provided with a window 20 with two different opening widths, a hole 21 configured to receive a probe 7 and a recess 24 configured to house a numbered cylindrical ring 5; further holes can be made on the bushing 3 for fixing at least one shaped plate 10 by means of suitable pins 8.

In particular, for two different widths of opening, the window 20 has a shape comprising two openings adjacent to each other and each having a different width from the other.

In other words, the window 20 has a first slot with a first width and a second slot, which is adjacent to the first slot and which is provided with a second width, greater than the first width.

The charging body 4 of the device 1 is the movable portion which is rotated during the charging phase of a predetermined number of revolutions (each revolution corresponds to two units of loaded drug and, in case of insulin, one unit corresponds to 10 microliters, although drugs with different units can have different values depending on the diameter of the piston 33 and on the pitch of the screw 30).

The shape of the charging body 4 also has the advantage of increasing the rotation arm in the charging phase, thus reducing the force required for said operation, and is also provided for housing supports for ampoules and/or vials.

The cylindrical ring 5 is inserted into the recess 24 of the bushing 3 and is free to move; furthermore, the cylindrical portion of the ring 5 is divided into two parts, of which a lower portion 25 (the one that appears from the smaller portion of the window 20, i.e. its first slot) has a plurality of n numbers, suitable spaced and with reference notches 11 , while the upper portion 26 has a dowelling surface which makes simple to move said ring 5 from the outside by a user, through the second slot of the window 20. A plurality of conical imprints, the number of which is equal to the number obtained in the portion 25, are provided on the lower cylindrical base of the ring 5 and said conical imprints 28 are engaged by the probe 7, which is fixed in the bushing 3 and which exactly allows to place the ring 5 in correspondence of the desired number; the angular position of the probe 7 in the bushing 3 is out of phase by an angle with respect to the axis of the window 20 which is equal to (2m + 1 )^*360 2n, where m is an integer number (so as to correctly show the numbers) and, moreover, the conical imprints 28 have a dimension such as to be, along the positioning diameter of the tip of said probe 7, in a perfect continuity between them, so that the numbered ring 5 can be positioned only between the axis of the probe 7 and the axis of the closest conical imprint 28.

A plurality of conical imprints 38 (the number of which is equal to the number of the conical imprints 28) are also provided in the upper cylindrical base of the numbered ring 5; said conical imprints 38 have the axis of the cone which is placed in correspondence of the axis of the cone of the imprints 28 of the lower base, but they have different dimensions of the cone's base and height; said upper conical imprints 38 are engaged by a special probe 9, which is placed inside a suitable hole performed in the movable part 4 of the device 1 and which is positioned parallel and on the opposite side with respect to the probe 7.

In particular, as shown in fig. 3, the probe 9 has a movement axis which is parallel to the axis of the probe 7, which is in turn substantially parallel to the axis of the charging body 4, with the advantage of occupying a smaller space compared to other known configurations of probes within drugs transdermic dosing devices according to the prior art.

The numbered portion 25 of the cylindrical ring 5 should have the numbers and the reference marks 1 1 placed exactly between the axes of the adjacent conical imprints 28 and 38.

The probe 9, when the movable part 4 of the device 1 rotates during the loading phase of the drug, slides on the shaped plate 10 until it meets the shaped radial windows 34, which are formed in diametrically opposite positions of the shaped plate 10; said angular or radial windows 34 have a suitable opening angle, which is able to exactly contain two complete upper conical imprints 38; moreover, said angular windows 34 are positioned, by means of the pins 8, with an angle between the center of the window 34 and the axis of the window 20 which is equal to a multiple of the angle 360 n (in the following description said angle is equal to 0° for sake of simplicity).

When the probe 9 meets the radial window 34, said probe 9 gets off the disc 10 and engages the numbered ring 5 in the upper portion 26 (imprint 38 formed in the upper base of the ring 5); therefore, since the axis of the probe 9 is aligned with the axis of the upper conical imprint 38, the numbered ring 5 is moved up and dragged by the probe 9 and covers an arc of circumference equal to the distance between the upper conical imprints 38 and the lower conical imprints 28 (that is to say equal to 360° divided by the number of the total conical imprints 28, 38), thus shifting exactly the ring 5 of an angle of the center distance between the imprints 28, 38 and moving forward a new number in the first slot of the window 20 of the bushing 3.

Once the probe 9 has traveled the angle of the center distance between two successive conical imprints 38, it meets the shaped edge of the disc 10, so that the probe 9 disengages from the ring 5.

In this way, at every 180° rotation of the movable part 4 of the device 1 , the numbered ring 5 is shifted by one step and the window 20 indicates the actual amount of the loaded drug; when the number of expected amounts or doses of the loaded drug is reached, it is possible to perform the injection using the button 22; finally, the resetting of the device 1 is made by slightly rotating the movable part 4 in the opposite direction with respect to the charging phase until the device 1 opposes a clear strength. Said strength is due to the use of an anti-rotation or anti-unscrewing system, which must allow minimum rotations of the movable part 4 (maximum of 10° from the engagement point) and which can be made as shown in the enclosed figs. 20 and 21 , i.e. by making a suitable finishing throat 35 on the thread of the punch 31 and by providing a possible E-ring 36 (fig. 21) or by providing the screwing and the clamping of a threaded screw 39 (fig. 20) on the screwed punch 31.

As described above, the special probe 9 slides on the shaped plate 10 thus disengaging the numbered ring 5 and, due to the dowelling surface of the upper portion 26, the ring 5 can be returned to its initial position.

The invention thus realized allows to make the drug's doses charging system in a very simple and easy way and easy to manage by the user, as well as significantly more accurate with respect to the known art, because it is also possible to predict a pre-loading value so as to consider loading and charge injection systematic errors and, moreover, it is also possible to measure fractions of units of the drug (i.e. half a unit or a quarter of a unit). The device 1 according to the invention also solves an objective problem that is encountered usually in the loading phase of the liquid drug.

In fact, as previously described, in order to load the liquid drug, the device 1 requires that the container or an adapter is able to drill the rubber cap of the drug's vial, so as to suck the liquid inside.

However, the inlet conduit (very narrow) is not filled with liquid and therefore, during the suction phase, a certain amount of air (instead of liquid drug) is inserted in the device 1 ; since we are dealing with a metering device, this involves an obvious error, as the device 1 does not contain a certain amount of drug which, however, is counted by the dosing meter.

In order to obviate said problem during the loading phase of the device 1 , as well as to remedy to additional systematic errors during the injection phase, the actual value of said errors has been statistically checked and a value of pre-loading able to correctly offset the value of said systematic errors has been defined.

Therefore, in order to load the right amount of liquid drug, it was considered that it is necessary to rotate the screw 30 of a certain value, taking into account that the corresponding value given by the volume of retraction of the piston 33 will not be injected; then, it was determined that the charging system does not start from zero but from a prefixed pre- loading value P different from zero, which is to be displayed in the window

20 of the loaded doses; operationally, when the device 1 has completed the pre-loading corresponding to said value P, the numbered ring 5 automatically switches to zero and it is possible to continue the operation by loading the required doses.

As said, the pre-loading value P takes into account, besides the error during the loading phase, the presence of other systematic errors, such as for example those linked to the fact that, for each injection, a certain amount of liquid drug is still not ejected; using the pre-loading value is thus enhanced the accuracy of the amount of the drug which is loaded and/or injected by the device 1.

Practically, considering that the pre-loading value is known (said value being expressed in microliters, which may be transformed into a predetermined angle of rotation of the movable part 4 of the device 1), it is possible to lock the movable part 4 on the holder assembly (nut) in correspondence of the point of engagement of the screw 30 on the nut, thus allowing the rotation of the nut and therefore the retraction of the piston 33.

The locking of the movable part 4 on the holder assembly (practicable, for example, by means of toothed male/female profiles) can be made in an arbitrary way, given the axial symmetry of the coupling system; in particular, it is usually done in a manner such that a suitable angle between the direction passing through the center of the window 20 and the axial direction of the probe 9 can be defined.

Considering a pre-load expressed by a given angle a and considering for convenience the angle between the angular window 34 and the axis of the window 20 equal to 0°, the point of engagement is to be moved by an angle, with respect the axis of the angular window 34, in an opposite direction with respect to the loading rotation, equal to a-360 2n.

Therefore, once the movable charging body 4 is moved back up to a position of anti-unscrewing and once the ring 5 (disengaged by the probe 9) is placed in a position of pre-loading P, it is possible to rotate the movable part 4 passing through the engagement point and from this point it is possible to perform the angular rotation a-360 n, so that the probe 9, at this point, engages the numbered ring 5 and drags said ring 5 for an angle equal to 360 n, by switching the number on the window 20 from the value P to the value 0, while a further rotation disengages the numbered ring 5 and engages it again after an angle equal to 180°-360 n, before triggering the value 1 on the portion 25 after exactly 180°.

If a further ring 6 is added between the numbered ring 5 and the movable part 4 of the device 1 , it is also possible to measure fractions of units, such as quarter and half units of drug.

This monitoring activity is done by providing on the ring 6 two notches (for half units) or four notches (for quarter units), which are suitably spaced and which have different heights depending on their position; in particular, it is possible to provide for two main notches regularly spaced with a maximum height, two notches offset by 90° with respect to the main notches and with an intermediate height (for indicating the half units) and four notches of lesser height in an intermediate position and out of phase by 45° (for indicating the quarter units). The ring 6 is fixed to the movable part 4 of the device 1 in a suitable position, so that a main notch of the ring 6 matches the indicator number of the loaded doses.

When, from an exact number of units (i.e. when it is just triggered a new number), the movable part 4 and the ring 6, integral with the part 4, are rotated, sequentially said movable part 4 and said ring 6 match a minimum notch (indicating +1/4 unit), a notch of intermediate height (indicating +1/2 unit) and again a minimum notch (indicating +3/4 unit).

This system is extremely simple and effective, since, at very low cost, solves the problem of displaying the drug's doses, allowing to manage both half units and quarters of a unit of drug (a very important feature when the drug is dispensed for children).

In a further advantageous manner, the device 1 according to the present invention is provided with at least one metallic fork 12, which is introduced in the movable part 4, through suitable grooves 13 provided on the movable part 4 and other similar grooves 14 provided on the cap 15 inserted in the fixed part 2 of the device 1.

In fact, the device 1 , during the atomizing step, is in practice composed of a movable part 4 and of a fixed part 2 and is held together only by an O- ring 16, which joins the movable part 4 with the cap 15 of the fixed part 2 and, in some situation of incorrect use (for example, injections without liquid), the thrust forces that are able to separate the movable part 4 from the fixed part 2 may be so strong to detach the O-ring 16 by the movable part 4, resulting in a separation of parts and breakage of the device 1. The insertion of the metallic fork 12 also solves this problem, since, even in case of incorrect use of the device 1 , said device 1 remains undamaged and operating.

The technical features of the drugs transdermic dosing device, which is the object of the present invention, as well as the related advantages, are clear from the above description.

Finally, it is also clear that other variations may be made to the device of the invention, without departing from the principles of novelty of the appended claims, as well as it is also clear that in the practical implementation of the invention, the materials, forms and dimensions of the details illustrated may be any according to requirements and these may be replaced with other technically equivalent.

Claims

1 . Drugs transdermic dosing device (1 ), comprising a body or fixed portion (2), which has a piston (33) and a nozzle (37) for dosing a drug, a movable or swiveling portion (4), associated with said fixed portion (2) and usable to set the dose of drug, and at least one button (22) for activating the device (1 ), which is connected with a punch (31 ) acting on said piston (33), characterized in that a bushing (3) is placed between said fixed portion (2) and said movable portion (4), said bushing (3) having a window (20) with two different widths of opening and with at least one internal seat or recess (24) for housing at least one cylindrical ring (5), which is free to move and which is divided into a lower portion (25), visible from an opening smaller than said window (20) and having a plurality of numbers and reference notches (1 1), and an upper portion (26), visible from outside and having a dowelling surface which is accessible by a user, through an opening greater than said window (20), said cylindrical ring (5) having a lower base, where there are formed a plurality of first conical imprints (28), said first conical imprints (28) being present in a number equal to the number of conical imprints provided in said lower portion (25) of the cylindrical ring (5) and adapted to be engaged by a first probe (7), permanently mounted in the bushing (3), and an upper base, where there are formed a plurality of second conical imprints (38), said second conical imprints (38) being present in a number equal to the number of said first conical imprints (28) and having respective axes placed in correspondence of the axes of said first conical imprints (28) and different dimensions with respect to said first conical imprints (28), said second conical imprints (38) being adapted to be engaged by a second probe (9), mounted within said movable portion (4) of the device (1 ) and placed parallel and opposite to said first probe (7).

2. Device (1 ) according to claim 1 , characterized in that said first conical imprints (28) have a continuous path, so that said cylindrical ring (5) can be positioned only in correspondence between the axis of said first probe (7) and the conical axis of the nearest imprint (28).

3. Device (1 ) according to at least one of the preceding claims, characterized in that, during a dosing phase of the drug, said second probe (9) slides on a disk (10), which is fixed on said bushing (3) and which has at least two radial windows (34), formed in diametrically opposite positions of said disk (10) and having a predetermined angular aperture, so as to contain two of said second conical imprints (38).

4. Device (1 ) according to at least one of the preceding claims, characterized in that when said second probe (9) is in correspondence with said radial windows (34) has an axis which is aligned with the axis of each of said second conical imprints (38), so that said cylindrical ring (5) is driven by said second probe (9) and travels an arc of a circle equal to the distance between said second conical imprints (38) and said first conical imprints (28), that is to say equal to 360° divided by the number of said first and second conical imprints (28, 38), said cylindrical ring (5) being so displaced of an angle equal to the distance between said second and first conical imprints (28, 38), so that it appears a new number of said cylindrical ring (5) through said window (20) of said bushing (3), said second probe (9) disengaging from said cylindrical ring (5) once it has performed said arc of circle.

5. Device (1 ) according to at least one of the preceding claims, characterized in that said movable portion (4) includes a system of anti- rotation or anti-unscrewing, which is provided during at least one reset phase, after having carrying out a drug injection inside the patient's skin.

6. Device (1) according to claim 5, characterized in that said anti-rotation or anti-unscrewing system comprises a finishing groove (35) for inserting the thread of a injection punch (31 ), which is provided with a sealing ring (36), or a screw (39) for locking said threaded punch (31), said threaded punch (31 ) being connected, on one hand, to an activation button (22) of the device (1 ) and, on the other hand, to said piston (33) for dosing the drug.

7 Device (1 ) according to at least one of the preceding claims, characterized in that said movable portion (4) is provided for setting a value of pre-load (P) of said drug and for displaying said value on said window (20), said value of pre-load (P) being provided in order to compensate for errors in loading the device (1) and for other systematic errors and corresponding to a prefixed angle of rotation of said movable portion (4) with respect to a point of engagement of a threaded nut on said punch (31).

8. Device (1) according to at least one of the preceding claims, characterized in that a further ring (6) is placed between said cylindrical ring (5) and said movable portion (4) of the device (1), said further ring (6) having four or eight spaced notches and having different heights as a function of their position, in order to indicate the half and/or quarters of loading units or doses of the drug, said further ring (6) being fixed and integral with said movable portion (4) of the device (1), so that at least one notch of said further ring (6) is an indicator of the loaded doses of drug.

9. Device (1) according to at least one of the preceding claims, characterized in that at least one metal fork (12) is introduced inside a plurality of grooves (13) of said movable portion (4) and inside other corresponding grooves (14) provided on a cap (15) inserted into the fixed portion (2) of the device (1), said movable portion (4) being connected to said fixed portion (2) through at least one sealing ring (16) which connects the movable portion (4) with said cap (15) of the fixed portion (2).